A divergent transcriptional landscape underpins the development and functional branching of MAIT cells.

MR1-restricted mucosal-associated invariant T (MAIT) cells play a unique role in the immune system. These cells develop intrathymically through a three-stage process, but the events that regulate this are largely unknown. Here, using bulk and single-cell RNA sequencing-based transcriptomic analysis in mice and humans, we studied the changing transcriptional landscape that accompanies transition through each stage. Many transcripts were sharply modulated during MAIT cell development, including SLAM (signaling lymphocytic activation molecule) family members, chemokine receptors, and transcription factors. We also demonstrate that stage 3 "mature" MAIT cells comprise distinct subpopulations including newly arrived transitional stage 3 cells, interferon-γ-producing MAIT1 cells and interleukin-17-producing MAIT17 cells. Moreover, the validity and importance of several transcripts detected in this study are directly demonstrated using specific mutant mice. For example, MAIT cell intrathymic maturation was found to be halted in SLAM-associated protein (SAP)-deficient and CXCR6-deficient mouse models, providing clear evidence for their role in modulating MAIT cell development. These data underpin a model that maps the changing transcriptional landscape and identifies key factors that regulate the process of MAIT cell differentiation, with many parallels between mice and humans.

A novel cylindrical TE(2,1) mode converter.

A novel, compact arrangement for Ka-band mode couplers, which convert a rectangular waveguide TE(1,0) to cylindrical waveguide TE(2,1) mode, has been designed, constructed, and tested. The design features a set of longitudinal slots, positioned in regions of negligible current flow for the TE(2,1) mode, allowing its propagation to be preferentially favored, by suppression of the fundamental TE(1,1) mode. Numerical simulations and experimental measurements display good agreement, showing transmission of the intended TE(2,1) mode at levels of better than -5 dB, from a frequency of ∼37.5 to 41 GHz. Subsequent farfield measurements confirm the presence of the TE(2,1) mode, demonstrating good agreement when compared with analytical expectations. Such a device would be an ideal candidate for an application where mode purity, bandwidth, and ease of construction are of primary importance and where the transmission efficiency is of limited concern.

Prospective surveillance of women with a family history of breast cancer: auditing the risk threshold.

To evaluate current guidelines criteria for inclusion of women in special 'breast cancer family history' surveillance programmes, records were reviewed of women referred to Scottish breast cancer family clinics between January 1994 and December 2003 but discharged as at 'less than 'moderate' familial risk'. The Scottish Cancer Registry was then interrogated to determine subsequent age-specific incidence of breast cancer in this cohort and corresponding Scottish population figures. Among 2074 women, with an average follow-up of 4.0 years, 28 invasive breast cancers were recorded up to December 2003, where 14.4 were expected, a relative risk (RR) of 1.94. Eleven further breast cancers were recorded between January 2004 and February 2006 (ascertainment incomplete for this period). The overall RR for women in the study cohort exceeded the accepted 'cutoff' level (RR=1.7) for provision of special counselling and surveillance. The highest RR was found for the age group 45-59 years and this group also generated the majority of breast cancers. The National Institute for Clinical Excellence ('NICE') guidelines appear to be more accurate than those of the Scottish Intercollegiate Guidelines Network ('SIGN') in defining 'moderate' familial risk, and longer follow-up of this cohort could generate an evidence base for further modification of familial breast cancer services.

Experimental and theoretical studies of a coaxial free-electron maser based on two-dimensional distributed feedback.

The first operation of a coaxial free-electron maser (FEM) based on two-dimensional (2D) distributed feedback has been recently observed. Analytical and numerical modeling, as well as measurements, of microwave radiation generated by a FEM with a cavity defined by coaxial structures with a 2D periodic perturbation on the inner surfaces of the outer conductor were carried out. The two-mirror cavity was formed with two 2D periodic structures separated by a central smooth section of coaxial waveguide. The FEM was driven by a large diameter (7 cm), high-current (500 A), annular electron beam with electron energy of 475 keV. Studies of the FEM operation have been conducted. It has been demonstrated that by tuning the amplitude of the undulator or guide magnetic field, modes associated with the different band gaps of the 2D structures were excited. The Ka-band FEM generated 15 MW of radiation with a 6% conversion efficiency, in good agreement with theory.

Experimental study of coaxial free-electron maser based on two-dimensional distributed feedback.

The first experimental study of a coaxial free-electron maser (FEM) based on two-dimensional (2D) distributed feedback is presented. A new type of cavity formed with coaxial 2D surface photonic band gap structures was used. The FEM was driven by a large diameter (7 cm), high-current (500 A), annular electron beam of energy 475 keV. By tuning the amplitude of the undulator or guide magnetic field, modes associated with the different band gaps of the 2D structures were excited. The -band coaxial FEM generated 15 MW of radiation with a 6% conversion efficiency, in excellent agreement with theory.

Clinical evaluation of extract of Cajanus cajan (Ciklavit) in sickle cell anaemia.

The major pathology in sickle cell anaemia (SCA) is sickling of red cells due to the precipitation of reduced haemoglobin. We report our experience with extract of Cajanus cajan as a possible antisickling agent by determining changes, if any, in clinical and laboratory features of the disease in patients given the extract in a single-blind placebo-controlled study. One hundred patients with steady-state SCA were randomized into treatment and placebo arms. The extract/placebo were administered twice daily to the subjects. Weight, hepatosplenomegaly, blood levels of biliurubin, urea, creatinine, and packed cell volume (PCV) were monitored over a 6-month period. Recall episodes of pain 6 months before enrolment were compared with episodes of pains recorded during the treatment period. Twenty-six cases (55.3 per cent) had hepatomegaly on enrolment. This significantly reduced to 33.3 per cent at 6 months (p = 0.03); but increased in the placebo arm (p > 0.05). The total number of recall painful episodes in cases was 207 (mean 4.4 +/- 10.3 (SD), range 0-60) and fell to 191 (mean 4.2 +/- 4.4 (SD), range 0-16); p = 0.03. Episodes of pain increased from 109 in controls (mean 2.6 +/- 5.0 (SD), range 0-26) to 164 (mean 3.9 +/- 4.3 (SD), range 0-22); p = 0.01. Mean PCV in the cases showed no appreciable changes (p = 0.1) but there was a significant increase in the controls (p = 0.02). In conclusion, the extract may cause a reduction of painful crises and may ameliorate the adverse effects of sickle cell anaemia on the liver. The mechanism of action remains to be determined.

Dispersion of helically corrugated waveguides: analytical, numerical, and experimental study.

Helically corrugated waveguides have recently been studied for use in various applications such as interaction regions in gyrotron traveling-wave tubes and gyrotron backward-wave oscillators and as a dispersive medium for passive microwave pulse compression. The paper presents a summary of various methods that can be used for analysis of the wave dispersion of such waveguides. The results obtained from an analytical approach, simulations with the three-dimensional numerical code MAGIC, and cold microwave measurements are analyzed and compared.

Factors associated with size and proportionality at birth in term Jamaican infants.

The objective of this study was to identify the factors associated with size and proportionality at birth in a cohort of term infants established to investigate their growth and development. One hundred and forty term low-birth-weight (birth-weight < 2,500 g) infants and 94 normal birth-weight infants (2,500- < 4,000 g) were recruited within 48 hours of birth at the main maternity hospital, Kingston, Jamaica. Birth anthropometry and gestational age were measured, and maternal information was obtained by interview and from hospital records. Controlling for gestational age, variables independently associated with birth-weight were rate of weight gain in the second half of pregnancy, maternal height, haemoglobin level < 9.5 microg/dL, time of first attendance in antenatal clinic, birth order, pre-eclampsia, and consumption of alcohol, with 33% of the variance in birth-weight explained. Birth length was associated only with maternal height and age, while measures of proportionality (ponderal index and head/length ratio) were associated with characteristics of the environment in late pregnancy, including rate of weight gain, weight in late pregnancy, and pre-eclampsia. The variation in maternal characteristics associated with size or proportionality at birth may reflect the times during gestation when different aspects of growth are most affected.

Factors associated with term low birth weight at Victoria Jubilee Hospital

OBJECTIVES: To examine factors associated with low birth weight (LBW) in term infants as part of a longitudinal study on the effects of term LBW. METHODS: Term LBW and normal birth weight (NBW) infants were recruited from the Victoria Jubliee Hospital, Kingston, Jamaica, between March and October, 1999. All LBW infants meeting the recruitment criteria were enrolled. The next eligible NBW infant of the same gender was enrolled for two of every three LBW infants. Gestational age was determined by the Dubowitz method. Anthropometric measurements were made and a questionnaire administered to determine maternal characteristics and antenatal history. Maternal height was measured and socioeconomic status assessed at home one week later. RESULTS: A total of 234 term infants (140 LBW and 94 NBW) were enrolled. There were no significant differences between the groups in maternal age, height, education, occupation or socioeconomic status. Mothers who reported alcohol consumption during pregnancy were more likely to have a LBW infant (Odds Ratio (OR) 2.26; 95 percent CI 1.01, 5.05) LBW infants were more likely to be first born (OR 1.73; 95 percent CI 1.01, 2.97). Mothers who had a previous LBW infant were at increased risk of having another LBW infant (OR 4.89; 95 percent CI 2.21, 10.84). CONCLUSION: Socioeconomic factors did not distinguish mothers at the Victoria Jubliee Hospital, who were likely to have a term LBW infant. Primiparous mothers and mothers who have given birth to a previous LBW infant are at risk of having a LBW infant and need special attention during the antenatal period.(Au)

The role of propionate and acetate in the control of food intake in sheep.

Sheep fed ad lib. on a good-quality pelleted diet (g/kg; hay 500, barley 300, molasses, fish meal and minerals) were infused via the hepatic portal vein with mixtures of the sodium salts of volatile fatty acids, acetate and propionate, and a variety of equivalent osmotic loads. Propionate infused at rates between 0.6 and 2.5 mmol/min consistently reduced food intake in a linear, dose-related manner. Propionate infusions resulted in consistent dose-related increases in peripheral venous plasma glucose concentration but variable changes in insulin concentration. Infusion of osmotically balanced mixtures of propionate, acetate, mannitol or saline (9 g NaCl/l) indicated that at constant osmotic loading propionate caused a greater reduction in intake than other infusions. Acetate infusions only depressed food intake when administered as a 1 M solution. Lower concentrations had little effect, similar to that of equivalent osmotic loads of mannitol or saline. It is concluded that portal propionate flow has a potential role in the control of food intake in ruminants which is independent of osmotic effects or changes in plasma insulin concentration.

Selective induction and inhibition of the components of 7-ethoxycoumarin O-deethylase activity in the rat.

Treatment of rats with 3-methylcholanthrene increased Vmax of the high-affinity component of 7-ethoxycoumarin O-deethylase activity 60-fold. There was also an increase in Vmax of the low-affinity component. Treatment with phenobarbitone increased Vmax of the high-affinity component six-fold whilst not affecting the Km of this component. Modest changes were also observed in the kinetics of the low-affinity component. Following treatment with 3-methylcholanthrene, the sensitivity of both the high- and low-affinity components of activity to inhibition by alpha-naphthoflavone was considerably increased, with the IC50 decreasing from greater than 250 microM to less than 10 microM in both instances. Following treatment with phenobarbitone, the sensitivity of the low-affinity component to inhibition by metyrapone was considerably increased, with the IC50 decreasing from greater than 1000 microM to 96 microM. There was also a modest, but significant, increase in sensitivity of the high-affinity component to metyrapone. These results indicate that both components of 7-ethoxycoumarin O-deethylase activity are catalysed by more than one form of cytochrome P-450.

Tissue differences in the ontogeny of inducibility of drug-metabolizing enzymes by 3-methylcholanthrene in the rabbit.

1. The effects of treatment of rabbits of different ages with 3-methylcholanthrene on cytochrome P-450 content, and benzo[a]pyrene hydroxylase, epoxide hydrolase, glutathione S-epoxide transferase, 1-naphthol glucuronyl transferase and morphine glucuronyl transferase activities of liver, kidney and lung have been investigated. 2. The cytochrome P-450 content of liver and kidney was inducible at all ages, whereas that of lung was inducible up to only seven days old. Benzo[a]pyrene hydroxylase activity was inducible more than two-fold in kidney at all ages, but in liver and lung up to only seven days old. 3. Epoxide hydrolase activity was inducible, only in liver and lung of younger animals, to an extent of less than 50%. 4. Glutathione S-epoxide transferase activity was inducible, in the liver of young animals and in the kidney of adult animals, to extents of less than 50%. 5. Both 1-naphthol and morphine glucuronly transferase activities were significantly induced in the liver of animals up to three days old, the former being induced to the greater extent. These enzymes were not studied in kidney or lung. 6. It is concluded that 3-methylcholanthrene treatment of rabbits has tissue-specific and age-specific effects on various drug-metabolizing enzyme.

Types of countertransference identified by Q-analysis.

It is suggested that the term countertransference is the name of a family of emotional responses experienced by psychotherapists during their personal interaction with a patient. Although such responses have a very special importance in the psychotherapeutic relationship, similar phenomena occur in all relationships. In this study, therefore, the feelings that each of the nurses on a psychiatric ward experienced during their conversations with 10 of the patients on that ward were investigated. With the help of the new mathematical technique of Q-analysis it was possible to identify a number of different types of response within a nurse's total reaction to a patient. These were called the role response, the diagnostic response, the character response and the conflict response. It is argued that it is more useful to try and identify and describe the different kinds of response that a therapist may have to a patient than to argue about what can and what cannot be legitimately called countertransference.

Biphasic O-deethylation of phenacetin and 7-ethoxycoumarin by human and rat liver microsomal fractions.

Human and rat liver microsomal fractions exhibit non-linear Michaelis-Menten kinetics in the O-deethylation of both phenacetin and 7-ethoxycoumarin. Comparison of various models indicated that the data were best described by a biphasic plot, which could be interpreted in terms of two populations of cytochrome P-450. The K(m)'s of the high affinity phase of 7-ethoxycoumarin O-deethylase activity were 1.8 +/- 0.4 microM and 2.3 +/- 0.4 microM for human and rat respectively while the K(m)'s of the low affinity phase were 205 +/- 20 microM and 237 +/- 59 microM in the two species respectively. V(max) of the high affinity phase of human 7-ethoxycoumarin O-deethylase activity was 96.9 +/- 19.0 pmol mg(-1) min(-1) and the activity of the corresponding phase in the rat was 2.7 times greater. The activities of the low affinity phase were 10-15 times greater than the respective activity of the high affinity phase. Rat and human also had similar values for the K(m)'s of the two phases of phenacetin O-deethylase activity, around 5 microM for the high affinity phase and 300 microM for the low affinity phase. Total activity was very similar in the two species, 1500-1750 pmol mg(-1) min(-1) and the difference between the two phases of activity was only 2.5-fold in man and 10-fold in rat. Studies on the effects of the in vitro modifiers of monooxygenase activity alpha-naphthoflavone and metyrapone further supported the hypothesis that the two phases of O-deethylase activity represent two different forms or populations of cytochrome P-450.